The present invention relates generally to means and method whereby ions from an ion source are selectively transmitted through a multipole apparatus having the capability of producing ion fragments via collisions with a surface or a gas to be readily analyzed by a TOF mass spectrometer. More specifically, a method and apparatus are described which use a plurality (preferrably three) of multipole devices, a collision surface (for SID), and/or a collision gas (for CID) to produce fragment ions of a selected m/z range for subsequent mass analysis.
The present invention relates to a multipole ion system with a collision surface for use in TOF mass spectrometry. The methods for transmitting ions and producing ion fragments described herein are enhancements of the techniques that are referred to in the literature relating to mass spectrometry.
Mass spectrometry is an important tool in the analysis of a wide range of chemical compounds. Specifically, mass spectrometers can be used to determine the molecular weight of sample compounds. The analysis of samples by mass spectrometry consists of three main stepsxe2x80x94formation of gas phase ions from sample material, mass analysis of the ions to separate the ions from one another according to ion mass, and detection of the ions. A variety of means exist in the field of mass spectrometry to perform each of these three functions. The particular combination of means used in a given spectrometer determine the characteristics of that spectrometer.
To mass analyze ions, for example, one might use a magnetic (B) or electrostatic (E) analyzer. Ions passing through a magnetic or electrostatic field will follow a curved path. In a magnetic field the curvature of the path will be indicative of the momentum-to-charge ratio of the ion. In an electrostatic field, the curvature of the path will be indicative of the energy-to-charge ratio of the ion. If magnetic and electrostatic analyzers are used consecutively, then both the momentum-to-charge and energy-to-charge ratios of the ions will be known and the mass of the ion will thereby be determined. Other mass analyzers are the quadrupole (Q), the ion cyclotron resonance (ICR), the time-of-flight (TOF), and the quadrupole ion trap analyzers.
Before mass analysis can begin, however, gas phase ions must be formed from sample material. If the sample material is sufficiently volatile, ions may be formed by electron impact (EI) or chemical ionization (CI) of the gas phase sample molecules. For solid samples (e.g. semiconductors, or crystallized materials), ions can be formed by desorption and ionization of sample molecules by bombardment with high energy particles. Secondary ion mass spectrometry (SIMS), for example, uses keV ions to desorb and ionize sample material. In the SIMS process a large amount of energy is deposited in the analyte molecules. As a result, fragile molecules will be fragmented. This fragmentation is undesirable in that information regarding the original composition of the samplexe2x80x94e.g., the molecular weight of sample moleculesxe2x80x94will be lost.
For more labile, fragile molecules, other ionization methods now exist. The plasma desorption (PD) technique was introduced by Macfarlane et al. in 1974 (Macfarlane, R. D.; Skowronski, R. P.; Torgerson, D. F., Biochem. Biophys. Res Commoun. 60 (1974) 616). Macfarlane et al. discovered that the impact of high energy (MeV) ions on a surface, like SIMS would cause desorption and ionization of small analyte molecules, however, unlike SIMS, the PD process results also in the desorption of larger, more labile speciesxe2x80x94e.g., insulin and other protein molecules.
Lasers have been used in a similar manner to induce desorption of biological or other labile molecules. See, for example, VanBreeman, R. B.: Snow, M.: Cotter, R. J., Int. J. Mass Spectrom. Ion Phys. 49 (1983) 35; Tabet, J. C.; Cotter, R. J., Anal. Chem. 56 (1984) 1662; or Olthoff, J. K.; Lys, I.: Demirev, P.: Cotter, R. J., Anal. Instrument. 16 (1987) 93. Cotter et al. modified a CVC 2000 time-of-flight mass spectrometer for infrared laser desorption of involatile biomolecules, using a Tachisto (Needham, Mass.) model 215G pulsed carbon dioxide laser. The plasma or laser desorption and ionization of labile molecules relies on the deposition of little or no energy in the analyte molecules of interest. The use of lasers to desorb and ionize labile molecules intact was enhanced by the introduction of matrix assisted laser desorption ionization (MALDI) (Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshica, T., Rapid Commun. Mass Spectrom. 2 (1988) 151 and Karas, M.; Hillenkamp, F., Anal. Chem. 60 (1988) 2299). In the MALDI process, an analyte is dissolved in a solid, organic matrix. Laser light of a wavelength that is absorbed by the solid matrix but not by the analyte is used to excite the sample. Thus, the matrix is excited directly by the laser, and the excited matrix sublimes into the gas phase carrying with it the analyte molecules. The analyte molecules are then ionized by proton, electron, or cation transfer from the matrix molecules to the analyte molecules. This process, MALDI, is typically used in conjunction with time-of-flight mass spectrometry (TOFMS) and can be used to measure the molecular weights of proteins in excess of 100,000 daltons.
Time-of-flight mass spectrometry (or TOFMS) plays an important role in the analysis of chemical compounds. Specifically, TOF mass spectrometers are useful in determining the molecular weight of sample compounds. In orthogonal TOF mass spectrometers ions pass from the source into the analyzer in a direction which is orthogonal to the axis of the analyzer. The concept of orthogonal acceleration using TOFMS was disclosed by O""Hallran et al. in 1964 (G. J. O""Halloran et al., Determination of Chemical Species Prevalent in a Plasma Jet. Technical Documentary Report No. ASD-TDR-62-664, prepared under contract AF 33(616)-8374 by the Bendix Corp. Research Laboratories (1964)). O""Hallran et al. also introduced the application of TOF mass analysis to ionization sources at elevated pressure. One advantage to using orthogonal acceleration and elevated pressure ionization sources is that ions form a continuous beam and can be mass analyzed more efficiently. Also, with the xe2x80x9corthogonal accelerationxe2x80x9d method, the mass analysis occurs along an axis which is orthogonal to the ion""s initial direction of motion. As a result, the initial energy of the ions does not significantly degrade the mass resolution of the instrument.
Chien and Lubman demonstrated the advantage of using a quadrupole ion trapxe2x80x94TOF mass analyzer in the analysis of electrospray produced ions (Chien, B. M.; Lubman, D. M., Anal. Chem. 66, 1630(1994)). The ions from the electrospray source are transferred with a high efficiency to the TOF analyzer and ions may be preselected and collision induced dissociation on these ions may be performed. One disadvantage with this method is low mass resolving power. Also, there are restrictions in the time required for cooling the ions and cycling the pressure in the ion trap.
Chernushevich et al discloses the use of ion introduction into an RF-quadrupole ion guide at a high gas pressure (I. V. Chernushevich, Proceedings of the 44th ASMS Conference of Mass Spectrometry and Allied Topics, May 12-16, 1173 (1996)). Similarly, Douglas discloses ion introduction into a quadrupole ion trap rather than a TOF analyzer (D. J. Douglas, U.S. Pat. No. 5,179,278). Here, the ions are cooled by passage through the quadrupole at elevated pressure and are then transferred into a low pressure region containing a quadrupole trap analyzer. This xe2x80x9ccollisional focusingxe2x80x9d method has also been incorporated with the xe2x80x9corthogonal accelerationxe2x80x9d method in TOF mass spectrometry to obtain a higher resolution mass spectrum.
Morris et al. discloses the use of additional multipole devices to preselect ions and induce collision dissociation in the trapxe2x80x94TOF analyzer (H. R. Morris et al., Rapid Comm. Mass Spectrom. 10, 889(1996)). Their first multipole device is used to cool ions then a second multipole is used for mass selection, and a third multipole is used for collision induced dissociation. Collision induced dissociation experiments were also disclosed in Lubman (B. M. Chien, S. M. Michael, D. M. Lubman, Int J. Mass Spectrom. Ion Process., 131, 149 (1994), B. M. Chien, D. M. Lubman, Anal. Chem. 66, 1630 (1994)).
Ions extracted from a multipole device and orthogonally accelerated in the direction of the axis of the analyzer will have a significant kinetic energy orthogonal to the axis of the analyzer. This initial kinetic energy will cause the ions to drift perpendicularly to the analyzer axis. This kinetic energy must be accounted for in order to prevent ion loss and to ensure ion detection. M. A. Park discloses a multideflector for correcting for such kinetic energies by deflecting the ion beam on the analyzer axis (U.S. Pat. Nos. 5,696,375 and 6,107,625).
Also, during the extracting process, the kinetic energy component of ions in the direction along the axis of the TOF analyzerxe2x80x94and therefore orthogonal to the axis of the multipole ion guidexe2x80x94will have a strong influence on the resolution that can be achieved by a TOF analyzer. To achieve best results, ions should be have near thermal kinetic energiesxe2x80x94achieved by cooling in the ion guide.
High efficiency in transmitting ions from a multipole to a TOF analyzer requires that the spatial extent of the ion beam perpendicular to the axis of the analyzer be large compared to, for example, that of prior art MALDI-TOF designs. As a result, some prior art devices (i.e. the two stage reflectron taught by R. Frye in U.S. Pat. No. 4,731,532) cannot be used with the orthogonal multipole orthogonal TOF instruments described above.
An alternative xe2x80x9cmethod and device for orthogonal ion injection into a time-of-flight mass spectrometerxe2x80x9d, proposed in Franzen U.S. Pat. No. 5,763,878 (the xe2x80x9cxe2x80x2878 patentxe2x80x9d). According to the xe2x80x2878 patent, ions are ejected from a multipole ion guide of design similar to that of Chernushevich et al. into a time-of-flight analyzer and in a direction orthogonal to the axis of the multipole device. In trapping mode an RF potential is applied to the poles of the multipole device whereas in ejection mode, DC potentials are applied to the poles of the multipole device so as to accelerate the ions in a direction orthogonal to the axis of the multipole device and parallel to the axis of the TOF analyzer.
Atmospheric pressure ionization (API) includes a number of methods. Typically, analyte ions are produced from liquid solution at atmospheric pressure. One of the more widely used methods, known as electrospray ionization (ESI), was first suggested by Dole et al. (M. Dole, L. L. Mack, R. L. Hines, R. C. Mobley, L. D. Ferguson, M. B. Alice, J. Chem. Phys. 49, 2240, 1968). In the electrospray technique, analyte is dissolved in a liquid solution and sprayed from a needle. The spray is induced by the application of a potential difference between the needle and a counter electrode. The spray results in the formation of fine, charged droplets of solution containing analyte molecules. In the gas phase, the solvent evaporates leaving behind charged, gas phase, analyte ions. Very large ions can be formed in this way. Ions as large as 1 MDa have been detected by ESI in conjunction with mass spectrometry (ESMS).
ESMS was introduced by Yamashita and Fenn (M. Yamashita and J. B. Fenn, J. Phys. Chem. 88, 4671, 1984). To establish this combination of ESI and MS, ions had to be formed at atmospheric pressure, and then introduced into the vacuum system of a mass analyzer via a differentially pumped interface. The combination of ESI and MS afforded scientists the opportunity to mass analyze a wide range of samples. ESMS is now widely used primarily in the analysis of biomolecules (e.g. proteins) and complex organic molecules.
In the intervening years a number of means and methods useful to ESMS and API-MS have been developed. Specifically, much work has focused on sprayers and ionization chambers. In addition to the original electrospray technique, pneumatic assisted electrospray, dual electrospray, and nano electrospray are now also widely available. Pneumatic assisted electrospray (A. P. Bruins, T. R. Covey, and J. D. Henion, Anal. Chem. 59, 2642, 1987) uses nebulizing gas flowing past the tip of the spray needle to assist in the formation of droplets. The nebulization gas assists in the formation of the spray and thereby makes the operation of the ESI easier. Nano electrospray (M. S. Wilm, M. Mann, Int. J. Mass Spectrom. Ion Processes 136, 167, 1994) employs a much smaller diameter needle than the original electrospray. As a result the flow rate of sample to the tip is lower and the droplets in the spray are finer. However, the ion signal provided by nano electrospray in conjunction with MS is essentially the same as with the original electrospray. Nano electrospray is therefore much more sensitive with respect to the amount of material necessary to perform a given analysis.
An elevated pressure ion source always has an ion production region (wherein ions are produced) and an ion transfer region (wherein ions are transferred through differential pumping stages and into the mass analyzer). The ion production region is at an elevated pressurexe2x80x94most often atmospheric pressurexe2x80x94with respect to the analyzer. The ion production region will often include an ionization xe2x80x9cchamberxe2x80x9d. In an ESI source, for example, liquid samples are xe2x80x9csprayedxe2x80x9d into the xe2x80x9cchamberxe2x80x9d to form ions.
Once the ions are produced, they must be transported to the vacuum for mass analysis. Generally, mass spectrometers (MS) operate in a vacuum between 10xe2x88x924 and 10xe2x88x9210 torr depending on the type of mass analyzer used. In order for the gas phase ions to enter the mass analyzer, they must be separated from the background gas carrying the ions and transported through the single or multiple vacuum stages.
The use of multipole ion guides has been shown to be an effective means of transporting ions through a vacuum system. Publications by Olivers et al. (Anal. Chem, Vol. 59, p. 1230-1232, 1987), Smith et al. (Anal. Chem. Vol. 60, p. 436-441, 1988) and Douglas et al. U.S. Pat. No. 4,963,736 (Douglas) have reported the use of AC-only quadrupole ion guides to transport ions from an API source to a mass analyzer. Such multipole ion guides may be configured as collision cells capable of being operated in RF only mode with a variable DC offset potential applied to all rods. Thomson et al., U.S. Pat. No. 5,847,386 (Thomson) also describes a quadrupole ion guide. The ion guide of Thomson is configured to create a DC axial field along its axis to move ions axially through a collision cell, inter alia, or to promote dissociation of ions (i.e., by Collision Induced Dissociation (CID)).
Further, mass spectrometers similar to that of Whitehouse et al. U.S. Pat. No. 5,652,427, entitled xe2x80x9cMultipole Ion Guide for Mass Spectrometryxe2x80x9d, (Whitehouse) use multipole RF ion guides to transfer ions from one pressure region to another in a differentially pumped system. In the source of Whitehouse, ions are produced by ESI or APCI at substantially atmospheric pressure. These ions are transferred from atmospheric pressure to a first differential pumping region by the gas flow through a glass capillary. Ions are transferred from this first pumping region to a second pumping region through a xe2x80x9cskimmerxe2x80x9d by an electric field between these regions as well as gas flow. A multipole in the second differentially pumped region accepts ions of a selected mass/charge (m/z) ratio and guides them through a restriction and into a third differentially pumped region. This is accomplished by applying AC and DC voltages to the individual poles.
A four vacuum stage ES/MS quadrupole mass spectrometer according to Whitehouse, incorporating a multipole ion guide beginning in one vacuum pumping stage and extending contiguously into an adjacent pumping stage, is depicted in FIG. 1. As discussed above, ions are formed from sample solution by an electrospray process when a potential is applied between spray needle 5 of sprayer 2 and sampling orifice 4. In other words, sample solution enters the ionization chamber through spray needle 5, at the end of which the solution is formed into a spray of fine droplets (not shown). The spray is formed as a result of an electrostatic field applied between spray needle 5 and sampling orifice 7. The sampling orifice may be an aperture, capillary, or other similar inlet leading into the differential pumping regions of the mass spectrometer. According to the prior art system shown in FIG. 1, capillary 16 is used to transport ions from atmospheric pressure region 1, where the ions are formed, to first pumping region 6. Lenses 10 and 14 are used to guide the ions from the exit end of capillary 16 through third pumping region 22 into a fourth pumping region 26 containing a mass analyzerxe2x80x94in this case a quadrupole mass analyzer.
Between lenses 10 and 30, an RF only hexapole ion guide 20 is used to guide ions through differential pumping stages 22 and 26 to exit 28 and into mass analysis region 32 through orifice 34. Ion guide 20 according to this prior art design is intended to provide for the efficient transport of ions from one location (i.e., the entrance of skimmer 14) to a second location (i.e., orifice 34). For the purpose of illustration, an electrospray ion source is shown as the API source. This could alternatively be an APCI or an ICP source.
Sample liquid is introduced through the electrospray needle 2 and is electrosprayedxe2x80x94either with or without pneumatic assistancexe2x80x94into chamber 1 as it exits needle 2. The charged droplets produced evaporate and desorb gas phase ions both in chamber 1 and as they are swept into vacuum through the annulus in capillary 16. A portion of the ions that enter first vacuum stage 6 through the capillary exit are focused through skimmer 14 with the help of lens 10 and the potential set on the capillary exit. Ions passing through skimmer 14 enter the multipole ion guide 20 which begins in vacuum pumping stage 22 and extends unbroken into vacuum stage 26. Ions falling within a certain m/z rangexe2x80x94determined in part by the frequency and amplitude of the potentials applied to ion guide 20xe2x80x94which enter multipole ion guide 20 will be guided to multipole ion guide exit end 28 and will be focused by exit lens 30 into the TOF analyzer region 32 through orifice 34 for subsequent analysis. Whitehouse also discloses the use of collisional gas within ion guide 20 to cool the ions to thermal velocities through collisional cooling.
In the scheme of Whitehouse, an RF only potential is applied to ion guide 20. As a result, ion guide 20 is not xe2x80x9celectivexe2x80x9d but rather transmits ions over a broad range of mass-to-charge (m/z) ratios. Such a range as provided by prior art multipoles is inadequate for certain applications, such as for Matrix Assisted Laser Desorption/Ionization (MALDI), because the ions produced may be well out of this m/z range. In other words, high m/z ions such as are often produced by the MALDI ionization method are often out of the range of transmission of conventional multipole ion guides.
Thus, electric voltages usually applied to the conventional ion guide are used to transmit ions from an entrance end to an exit end. Analyte ions produced in the ion production region pass through a capillary or other ion transfer device to move the ions to a differentially pumped region and enter the ion guide at the entrance end. Through collisions with gas in the ion guide, the kinetic energy of the ions is reduced to thermal energies. Simultaneously, the RF potential on the poles of the ion guide forces ions to the axis of the ion guide. Then, ions migrate through the ion guide toward its exit end, where the ions typically either enter a second ion guide or enter the mass analysis region.
Whitehouse also discloses use of two or more ion guides in consecutive vacuum pumping stages to allow different DC and RF values. However, losses in ion transmission efficiency may occur in the region of static voltage lenses between ion guides. For example, a commercially available API/MS instrument manufactured by Hewlett Packard incorporates two skimmers and an ion guide. The region between the skimmers is pumped by the drag stage of the same turbopump which pumps the region containing the multipole ion guide. That is, an additional pumping stage/region is added without the addition of an extra turbo pump, and therefore, improved pumping efficiency may be achieved. In this dual skimmer design, there is no ion focusing device between skimmers, therefore ion losses may occur as the gases are pumped away. A second example is demonstrated by a commercially available API/MS instrument manufactured by Finnigan which applies an electrical static lens between capillary and skimmer to focus the ion beam. Due to narrow mass range of the static lens, the instrument may need to scan the voltage to optimize the ion transmission.
In addition, the electrode rods of the prior art multipole ion guides described above are positioned in parallel and are equally spaced at a common radius from the centerline of the ion guide. Thus, ions with a m/z ratio that fell within the ion guide stability window established by the applied voltages would have stable trajectories within the ion guide""s internal volume bounded by the parallel, evenly spaced rods. This is true for quadrupoles, hexapoles, etc.
In other schemes a multipole might be used to guide ions of a selected m/z through the transfer region. For example, Morris et al., in H. R. Morris et al., High Sensitivity Collisionally Activated Decomposition Tandem Mass Spectrometry on a Novel Quadrupole/Orthogonal-Acceleration Time-of-Flight Mass Spectrometer, Rapid Commun. Mass Spectrom. 10, 889 (1996), use a series of multipoles in their design. One of these is a quadrupole. The quadrupole can be run in a xe2x80x9cwide bandpassxe2x80x9d mode or a xe2x80x9cnarrow bandpassxe2x80x9d mode. In the wide bandpass mode, an RF-only potential is applied to the quadrupole and ions of a relatively broad range of m/z values are transmitted. In narrow bandpass mode both RF and DC potentials are applied to the quadrpole such that ions of only a narrow range of m/z values are selected for transmission through the quadrupole. In subsequent multipoles, the selected ions may be activated towards dissociation. In this way the instrument of Morris et al. is able to perform MS/MS experiments with a first mass analysis and subsequent fragmentation occurring in what would otherwise be simply a set of multipole ion guides.
Such a prior art ionization source according to Morris et al. is shown in FIG. 2. This prior art source design is similar to Whitehouse (as shown in FIG. 1), except for the multipole ion guide arrangement. In the prior art source design according to Morris et al., four RF multipoles 48, 50, 52 and 54 are used. The first multipole encountered by the ions is hexapole 48. It is used in a manner similar to the Whitehouse et al. to cool and guide the ions. The second multipole encountered is quadrupole 50. Quadrupole 50 can be used in a wide bandpass mode to transmit ions over a broad m/z range, or in a narrow bandpass mode to transmit ions of a selected narrow m/z range. This leads to the use of the mass spectrometer instrument in MS and MS/MS modes. In MS mode, quadrupole 50 is operated as a wide bandpass ion guide. Ions are simply transmitted by all four multipoles 48, 50, 52 and 54 to time-of-flight mass analyzer 62. The TOF mass analyzer 62 is then used to produce a mass spectrum. In MS/MS mode, quadrupole 50 is operated as a narrow bandpass ion guide to select ions of interest.
Further, the ions encounter a third multipolexe2x80x94hexapole 52xe2x80x94which is operated with a DC offset with respect to quadrupole 50 and contains a collision gas. This leads to collisions between the ions of interest and the collision gas and can result in the formation of fragment ions. Finally, the fragment ions are guided by a fourth multipolexe2x80x94hexapole 54xe2x80x94to TOF analyzer 62 which is then used to produce a mass spectrum of these fragment ions.
In the performance of tandem mass spectrometry experiments, precursor ions are selected and fragmented, and the fragment ions are analyzed to produce a fragment ion spectrum. In the prior art, a variety of methods have been used to fragment precursor ions. Among these are collision induced dissociation (CID) as mentioned above, surface induced dissociation (SID), infrared multiphoton dissociation (IRMPD), electron capture dissociation (ECD), and many others. Each of these methods has its advantages and disadvantages. For example, CID is a relatively simple technique and can be applied in a variety of instrument configurations (i.e. quadrupole, TOF, or FT-ICR analyzers). IRMPD is somewhat more complex in that a laser is required, but has the advantage that it produces no gas load on the vacuum systemxe2x80x94as is the case in CIDxe2x80x94and can produce fragment species that are inaccessible by CID. SID is also somewhat complex in that it is necessary that a xe2x80x9ccollision surfacexe2x80x9d be prepared and placed in the instrument. Also, SID is not readily adaptable to all types of analyzers. However, SID does provides better control over the fragmentation process and can lead to higher efficiency in the production of useful fragment ions.
Quadrupole mass analyzers have been used in conjunction with surface induced dissociation (SID). For example, Wysocki et al. discloses such an arrangement (Chungang GU, Vincent J. Angelico, Vicki H. Wysocki, Proceedings of the 46th ASMS conference on Mass Spectrometry and Allied Topics, pg. 72(1998), Wysocki et al., Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics, pg. 2834, 2144, 1040, and 2299(1999), Ahok Dongre, Vicki Wysocki, Org. Mass Spectrom. 29, 700(1994), Thomas Kane, Vincent Angelico, and Vicki Wysocki, Langmuir 13, 6722(1997), Chungang Gu, Vicki Wysocki, J. AM. Chem. Soc. 119, 12010(1997), Arpad Somogyi, Thomas Kane, Jian-Mei Ding, Vicki Wysocki, J. AM. Chem. Soc. 115, 5275(1993), Thomas Kane, Vincent Angelico, Vicki Wysocki, Anal. Chem. 66, 3733(1994), Thomas Kane, Vicki Wysocki, Int. J. Mass. Spectrom. Ion Process 140, 177(1994), Vicki Wysocki et al., Am. Soc. Mass. Spectrom. 3, 27(1992)). In such an arrangement, as shown in FIG. 3, first quadrupole 81 comprising rods 80 is used to select ions of a given m/z from a beam of incoming ions 78. The selected ions are allowed to collide with a SID xe2x80x9ccollision surfacexe2x80x9d 76 after passing through electrodes 82. The instrument according to Wysocki can be operated without fragmentation of the selected ions or with surface-induced dissociation of the selected ions. In SID, the ions are dissociated via energetic collisions with a prepared xe2x80x9ccollision surfacexe2x80x9d. This collision results in the fragmentation of the selected ions into xe2x80x9cfragment ionsxe2x80x9d, and the fragment ions are extracted (and focused by electrodes 84) into second quadrupole 85 comprising rods 86. Second quadrupole 85 is used to analyze the these fragment ions.
In MS mode, or to produce simply a mass spectrum of the incident ion beam, first quadrupole 81 is scanned over the mass range of interest while second quadrupole 85 is operated in broad bandpass mode (i.e., RF only). The potential between the source (not shown) and collision surface 76 is held at zero volts. As a result, ions exiting first quadrupole 81 do not strike collision surface 76, but rather, these ions are deflected into second quadrupole 85 which transmits them to a detector (not shown).
In SID MS/MS mode, first quadrupole 81 is used to select ions of a given m/z out of the incident ion beam. These ions are allowed to strike collision surface 76. The kinetic energy of the ions when they strike surface 76 is determined largely by the potential difference between the ion source (not shown) and collision surface 76. Fragment ions resulting from the ion-surface collision are extracted by an electrostatic field into second quadrupole 85 where they are mass analyzed to produce a fragment ion spectrum.
For example, FIGS. 4A-D depict the operation of the O-SID-O instrument according to Wysocki without fragmentation due to SID (FIGS. 4A-B) and with fragmentation due to SID (FIGS. 4C-D). In MS mode, as shown in FIGS. 4A-B, no potential difference is applied between source 90 and collision surface 96. In this case, the ions are transmitted from source 90 through quadrupole 92, but do not strike collision surface 96 (as indicated by ion path 94) and do not produce fragment ions. The ions then enter quadrupole 98 for mass analysis. Therefore, because no fragment ions are produced, the resulting mass spectrum 120 shown in FIG. 4B contains a single peak 100xe2x80x94that of the incident beam.
In SID MS/MS mode, as shown in FIGS. 4C-D, a potential difference is applied between source 102 and collision surface 108. In this case, selected ions are transmitted from source 102 through ion guide 104, such that they strike collision surface 108 (at location 106 of the ion beam path). As a result of the collision, ion fragments of the initial ion beam are formed (as indicated at ion beam 110) and enter second quadrupole 112. Second quadrupole 112 is used to mass analyze the fragment ion. Once analyzed, these fragment ions then enter the detector (not shown). The resulting sharp peaks 114 of the mass spectrum 116 shown in FIG. 4D depicts multiple m/z values of the fragment ions.
The present invention provides means and method of using SID in conjunction with any mass analyzerxe2x80x94in the preferred embodiment, a TOF mass analyzer. More specifically, a first multipole (preferably a quadrupole) is used to select precursor ions, the ions are allowed to collide with a collision surface, and the fragment ions thereby produced are collisionally cooled in a second multipole and then mass analyzed in a mass analyzer (preferably a TOF mass analyzer). Further, a method and apparatus are described which use a plurality (preferably three) of multipole devices, a collision surface (for SID), and/or a collision gas (for CID) to produce fragment ions of a selected m/z range (i.e., using a Q-SID-Q or Q-CID-Q arrangement) for subsequent mass analysis (preferably in an orthogonal TOF mass analyzer).
The purpose of the present invention is to provide a tandem mass spectrometry instrument with improved performance characteristics over prior art instruments. Particularly, the preferred embodiment Q-SID-Q-TOF instrument according to the present invention is capable of surface induced dissociation, and collision induced dissociation. Thus, an instrument according to the present invention can be used to take advantage of the fragmentation characteristics of either of these methods. Also, because a TOF mass analyzer is used in the preferred embodiment, precursor and fragment ion spectra can be obtained rapidlyxe2x80x94i.e. on a time scale consistent with hyphenation of the instrument with liquid chromatography.
Another object of the present invention is to provide a means of adapting surface induced dissociation to any type of mass analyzer. That is, SID is performed between two mulitpolesxe2x80x94e.g. Q-SID-Qxe2x80x94followed by mass analysis in a mass analyzer of choicexe2x80x94e.g. FT-ICR, quadrupole trap, etc.
Other objects, features, and characteristics of the present invention, as well as the methods of operation and functions of the related elements of the structure, and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following detailed description with reference to the accompanying drawings, all of which form a part of this specification.